Comparison of peripheral and central administration of naloxone in precipitating abstinence in morphine-dependent...

Although it has been known that a morphine abstinence syndrome can be induced by naloxone administered centrally or peripherally, data on a detailed qualitative and quantitative comparison are not available. In the present study morphine pellets were implanted into rats and naloxone was administered intracerebroventricularly (i.c.v.) or subcutaneously (s.c.) 72 h later. A full array of abstinence signs with similar latency, duration, and intensity was seen in morphine-dependent rats following naloxone by either route. There were no major differences in the spectrum of withdrawal signs or in the proportion of rats showing the individual signs. In terms of body weight and temperature, the highest doses tested by each route produced similar quantitative effects. Our results demonstrate that naloxone given i.c.v. can precipitate the full morphine abstinence syndrome in rats at about 1/3 the dose needed for comparable effects when the antagonist is administered s.c.